Method and equipment for continuous and selective inclusion separation

ABSTRACT

In a reaction system having at least two liquid-liquid interfaces between an organic phase of raw material containing a compound(s) to be separated and an aqueous phase of an aqueous solution of inclusion-complexing agent and between that aqueous phase and an organic phase(s) of extraction solvent(s), the compound(s) to be separated is entrapped into the aqueous phase through formation of an inclusion complex(es) of the inclusion-complexing agent with the compound(s), while the compound(s) is entrapped into the organic phase(s) of extraction solvent(s) through dissociation of said inclusion complex(es). The foregoing operation is performed using, for example, a squarish U-shaped tube or an H-shaped tube with bottom plates. Preferred examples of inclusion-complexing agent include highly water-soluble branched cyclodextrins.

TECHNICAL FIELD

[0001] The present invention relates to a method of effectivelyseparating a variety of compound(s) as an object(s) of separation usefulas a starting material(s) of chemical syntheses and/or the like, and aseparator for use therein. Raw materials that can be subjected to themethod of the present invention are a wide variety of raw materials,examples of which include disubstituted benzene isomer mixtures such asxylene isomer mixtures, trisubstituted benzene isomer mixtures such astrimethylbenzene isomer mixtures, methylquinoline isomer mixtures,substituted naphthalene isomer mixtures such as methylnaphthalene isomermixtures and dimethylnaphthalene isomer mixtures, and optical isomermixtures of pinene, limonene, menthol, mandelic acid esters, etc.

BACKGROUND ART

[0002] Separation of compounds as objects of separation from rawmaterials as mentioned above is difficult or impossible by a customarydistillation or crystallization method, so that special separationmethods have been invented for and applied to respective raw materials.

[0003] The present inventors and the like had already discovered andpatented methods according to which compounds as mentioned above can behighly selectively separated using either an aqueous solution of highlywater-soluble substituted cyclodextrin such as branched cyclodextrin oran aqueous alkaline solution of unsubstituted cyclodextrin throughformation of inclusion complexes and subsequent liquid-liquidextraction. An organic compound(s) as an object(s) of separationentrapped in an aqueous solution of a cyclodextrin is contacted with anorganic solvent such as diethyl ether, or heated at a temperature of atleast 60° C., whereby the compound(s) can be dissociated from thecyclodextrin and recovered. However, a continuous process of treatmentsranging from entrapment of a compound(s) as an object(s) of separationin an aqueous solution of cyclodextrin to recovery thereof cannot easilybe established. This is not limited to a case where a cyclodextrin isused as one kind of inclusion-complexing agent.

[0004] Accordingly, an object of this invention is to provide acontinuous and selective method of entrapping a compound(s) as anobject(s) of separation into an aqueous phase made of an aqueoussolution of inclusion-complexing agent, and dissociating and recoveringthe entrapped compound(s) from the inclusion-complexing agent.Incidentally, the term “selective” used herein refers to a selectivitywith which there can be attained an improvement in the purity of acompound as an object of separation, which is sufficient enough toprovide a possibility of developing an industrially useful process.

DISCLOSURE OF THE INVENTION

[0005] The present invention provides a continuous and selectiveinclusion separation method characterized in that, in a reaction systemhaving at least two liquid-liquid interfaces between an organic phase ofraw material containing a compound(s) to be separated and an aqueousphase of an aqueous solution of inclusion-complexing agent and betweenthat aqueous phase and an organic phase(s) of extraction solvent(s), thecompound(s) to be separated is entrapped into the aqueous phase throughformation of an inclusion complex(es) of the inclusion-complexing agentwith the compound(s), while the compound(s) is entrapped into theorganic phase(s) of extraction solvent(s) through dissociation of theinclusion complex(es); and an inclusion separator characterized bycomprising a reaction vessel constructed so as to allow an aqueous phaseof an aqueous solution of inclusion-complexing agent to formliquid-liquid interfaces with at least two organic phases that are anorganic phase of raw material containing a compound(s) to be separatedand an organic phase(s) of extraction solvent(s), and stirring means forstirring at least neighborhoods of the respective liquid-liquidinterfaces. Incidentally, the reaction vessel may be provided with aheating and/or cooling means and/or pipings for feeding and/orwithdrawing the aqueous solution of inclusion-complexing agent, the rawmaterial and the extraction solvent(s) if necessary.

[0006] According to the present invention, a wide variety of rawmaterial, examples of which include disubstituted benzene isomermixtures such as xylene isomer mixtures, trisubstituted benzene isomermixtures such as trimethylbenzene isomer mixtures, methylquinolineisomer mixtures, substituted naphthalene isomer mixtures such asmethylnaphthalene isomer mixtures and dimethylnaphthalene isomermixtures, and optical isomer mixtures of pinene, limonene, menthol,mandelic acid esters, etc., may be contacted with an aqueous phase of anaqueous solution of, e.g., highly water-soluble cyclodextrin such as abranched cyclodextrin as an inclusion-complexing agent to form at leastan inclusion complex of the cyclodextrin with a compound contained inthe raw material and to be separated, while in parallel the aqueousphase is contacted with a wide variety of extraction solvent such asheptane to dissociate the inclusion complex, whereby the includedcompound can be recovered in the organic phase of extraction solvent.

[0007] In the present invention, one liquid-liquid interface of theaqueous phase of the aqueous solution of inclusion-complexing agent suchas a cyclodextrin is an interface with the organic phase of raw materialcontaining a compound(s) to be separated, so that inclusion complexes ofinclusion-complexing agent with compounds in the organic phase of raw amaterial may be yielded toward their formation in accordance withcomplex formation constants thereof to selectively entrap in the aqueousphase a at compound to be separated. And other liquid-liquidinterface(s) of the aqueous phase is an interface(s) with an organicphase(s) of extraction solvent(s), so that the compound(s) entrapped inthe aqueous phase and to be separated can be dissociated to be extractedin the organic phase(s) of extraction solvent(s). The foregoingoperation can be performed using a reaction vessel, examples of whichinclude a U-shaped tube that may be squarish as shown in FIGS. 1 to 3and an H-shaped tube with bottom plates (hereinafter referred to simplyas an “H-shaped tube” ) as shown in FIGS. 4 to 6 to which the reactionvessel is not limited. Various altered reaction vessels are usable aswill be described later.

BRIEF DESCRIPTION OF DRAWINGS

[0008]FIG. 1 is a conceptual cross-sectional view illustrating anexample of reaction vessel in the basic inclusion separator of thepresent invention that may be used in the method of the presentinvention.

[0009]FIG. 2 is a conceptual schematic cross-sectional view of aninclusion separator used in Examples 12 and 28.

[0010]FIG. 3 is a conceptual schematic cross-sectional view of aninclusion separator used in Examples 1 to 9, 11, 13 to 27, and 29 to 38.

[0011]FIG. 4 is a conceptual cross-sectional view illustrating anotherexample of reaction vessel in the basic inclusion separator of thepresent invention that may be used in the method of the presentinvention, and showing a state thereof wherein use is made of a rawmaterial higher in specific gravity than an aqueous phase and anextraction solvent lower in specific gravity than the aqueous phase.

[0012]FIG. 5 is a conceptual cross-sectional view illustrating anotherexample of reaction vessel in the basic inclusion separator of thepresent invention that may be used in the method of the presentinvention, and showing a state thereof wherein use is made of a rawmaterial lower in specific gravity than an aqueous phase and anextraction solvent higher in specific gravity than the aqueous phase.

[0013]FIG. 6 is a conceptual cross-sectional view illustrating anotherexample of reaction vessel in the basic inclusion separator of thepresent invention that may be used in the method of the presentinvention, and showing a state thereof wherein use is made of a rawmaterial and an extraction solvent both higher in specific gravity thanan aqueous phase.

EXPLANATION OF SYMBOLS

[0014]1, 11, 21 . . . U-shaped tube, 31, 41, 51 . . . H-shaped tube,

[0015]2, 22, 32, 42, 52 . . . diaphragm (not an indispensable element),

[0016]3, 13, 23, 33, 43, 53 . . . aqueous (cyclodextrin) phase,

[0017]4, 14, 24, 34, 44, 54 . . . organic phase of raw material,

[0018]5, 15, 25, 35, 45, 55 . . . organic phase of extraction solvent.

MODES FOR CARRYING OUT THE INVENTION

[0019] Modes for carrying out this invention will now be described, butshould not be construed as limiting the scope of the invention. Thefollowing description will be made with priority given to cases wherecyclodextrins are used as inclusion-complexing agents. However, it goeswithout saying that this invention is not limited to these cases inlight of the principle of the invention.

[0020] When the specific gravity of an organic phase of raw materiallike a xylene mixture is considerably lower than that of an aqueousphase of an aqueous solution of cyclodextrin (hereinafter often referredto briefly as an “aqueous cyclodextrin phase”), the organic phase of rawmaterial and an organic phase of extraction solvent may be respectivelystirred together with the aqueous cyclodextrin phase in a U-shaped tube,whereby inclusion complexation and dissociation-extraction can beeffected with improved contact efficiencies. On the other hand, when thespecific gravity of the organic phase of raw material is not so lowerthan or slightly higher than that of the aqueous cyclodextrin phase, theorganic phase of raw material is dispersed in or put under the aqueouscyclodextrin phase. When the organic phase of raw material is dissolvedinto the organic phase of extraction solvent, selective separation isnot effected as a matter of course. In this case, the aqueous phaseexisting between the organic phase of raw material containing acompound(s) to be separated and the organic phase of extraction solventmay be partitioned with a diaphragm permeable to the aqueous solutionbut hardly permeable to oily droplets to prevent the organic phase ofraw material dispersed in the aqueous cyclodextrin phase from migratinginto the organic phase of extraction solvent. Examples of the diaphragminclude filter paper, filter cloth, nonwoven fabric, net and textilemade of fibers of a material, examples of which include cellulose andderivatives thereof, rayon, hairy materials such as wool, silk,plastics, glass, silica, metals, etc.; porous plastic membranes; porousrigid plastic materials formed by sintering a plastic material; ceramicfilters formed by sintering ceramic fibers; and sintered stainlessfilters formed by sintering stainless steel fibers; provided that theymay optionally be treated so as to become oil-repellent. Apart from theforegoing case, use of the diaphragm can further improve the contactefficiencies because the organic phase of raw material and the organicphase of extraction solvent can be vigorously stirred together with theaqueous cyclodextrin phase, whereby the rates and efficiencies ofinclusion complexation and dissociation-extraction can be enhanced.After withdrawal of the organic phase of extraction solvent and additionof fresh extraction solvent, stirring and extraction may also becontinued afresh. Incidentally, where the specific gravity of rawmaterial and/or extraction solvent is higher than that of the aqueouscyclodextrin phase, the H-shaped tube as will be detailed later mayadvantageously be used. Where the specific gravity of the aqueouscyclodextrin phase is between those of the organic phases of rawmaterial and extraction solvent, an I-shaped tube with a bottom platemay also advantageously be used as the reaction vessel.

[0021] At least part of a solution as the organic phase of extractionsolvent containing a compound extracted thereinto as an object ofseparation may advantageously be withdrawn and distilled to concentratethe compound, and the organic solvent separated by distillation may bereturned back to the reaction system and reused as the extractionsolvent (see Example 27). In this case, the efficiency of extraction canbe enhanced because the extraction solvent is refreshed.

[0022] The foregoing inclusion complexation and dissociation-extractionoperation is performed preferably in the range of 0 to 50° C., morepreferably 5 to 40° C., further preferably 10 to 25° C.

[0023] Any aqueous phase of cyclodextrin will suffice insofar as it doesnot yield a solid substance when the cyclodextrin forms any inclusioncomplexes thereof with any organic compounds to be separated. Needlessto say, highly water-soluble substituted cyclodextrins such as branchedcyclodextrins can be used in the present invention. Even unmodifiedcyclodextrins may be used in the operation of the present invention ifthey are used in the form of an aqueous solution mixed with sodiumhydroxide, potassium hydroxide or the like for enhancing the watersolubilities thereof and hence enhancing the water solubilities of theresulting inclusion complexes without formation of any solid substance.

[0024] Examples of substituted cyclodextrins usable asinclusion-complexing agents in the present invention include substitutedcyclodextrins such as α-, β- or γ-cyclodextrin with at least onehydroxyl group thereof having its hydrogen atom substituted with atleast one selected from among a glucosyl group, a maltosyl group,maltooligosaccharide residues, a methyl group, a hydroxyethyl group,hydroxypropyl groups, a sulfonic group, alkylenesulfonic groups, andcarboxyalkyl groups. Herein, the term “sulfonic group” is intended toencompass not only a group in the free acid form but also groups in asalt form of sodium, potassium, ammonium, lower amine, ethanolamine orthe like. The “carboxyl moiety” of “carboxyalkyl group” is intended tohave the same meaning as the “sulfonic group.” The alkylene moiety ofalkylenesulfonic group may be either linear or branched, and ispreferably 1 to 5 in the number of carbon atoms. The alkyl moiety ofcarboxyalkyl group may be either linear or branched, and is preferably 1to 5 in the number of carbon atoms. Preferred specific examples ofusable cyclodextrins include monoglucosyl-α-cyclodextrin,diglucosyl-α-cyclodextrin, triglucosyl-α-cyclodextrin, and mixturesthereof; monomaltosyl-α-cyclodextrin, dimaltosyl-α-cyclodextrin,trimaltosyl-α-cyclodextrin, and mixtures thereof;monoglucosyl-β-cyclodextrin, diglucosyl-β-cyclodextrin,triglucosyl-β-cyclodextrin, and mixtures thereof;monomaltosyl-β-cyclodextrin, dimaltosyl-β-cyclodextrin,trimaltosyl-β-cyclodextrin, and mixtures thereof;2,6-dimethyl-α-cyclodextrin; and 2,6-dimethyl-β-cyclodextrin.

[0025] The suitable cyclodextrin concentration is preferably 5 to 50 wt.%, further preferably 5 to 30 wt. %, based on the aqueous solution.

[0026] Examples of raw materials that can be subjected to selectiveseparation with the aid of a cyclodextrin include indole-containingmixtures (Japanese Patent Laid-Open No. 2-200671); disubstituted benzeneisomer mixtures such as xylene isomer mixtures, dichlorobenzene isomermixtures, nitrotoluene isomer mixtures, and chlorobenzotrifluorideisomer mixtures (Japanese Patent Laid-Open Nos. 3-184925 and 6-287149);trisubstituted benzene isomer mixtures such as trimethylbenzene isomermixtures, trichlorobenzene isomer mixtures, dimethylnitrobenzene isomermixtures, chloronitrotoluene isomer mixtures, dinitrotoluene isomermixtures, and xylenol isomer mixtures (Japanese Patent Laid-Open No.6-87765); 2-methylquinoline-containing hydrocarbon oils (Japanese PatentLaid-Open No. 2-255658); 7-methylquinoline-containing mixtures (JapanesePatent Laid-Open No. 4-321668); 2,6-diisopropylnaphthalene-containingmixtures (Japanese Patent Laid-Open Nos. 2-204419 and 2-209818);2-methylnaphthalene-containing mixtures (Japanese Patent Laid-Open No.2-255630); 2,6-dimethylnaphthalene-containing mixtures (Japanese PatentLaid-Open No. 6-116179); and optical isomer mixtures of pinene,limonene, menthol, mandelic acid esters, etc. Incidentally, in the caseof raw materials having a determined composition like mixed xylene, thepurity of a given compound in the residual organic phase of raw materialafter subjected to the method of the present invention is improved, sothat the residual organic phase of raw material may be repeatedlysubjected as raw material to the method of the present invention,whereby that purity can be improved to a desired level.

[0027] The amount of the organic phase of raw material containing acompound to be separated is preferably such that the molar ratio of thecompound to a cyclodextrin in the aqueous cyclodextrin phase is at leastone. Where the raw material is a solid substance, it can be subjected inthe form of a solution to separation after it is dissolved in a suitableorganic solvent hardly capable of being included in the cyclodextrin.

[0028] Organic solvents hardly soluble in water and hardly capable offorming an inclusion complex with a cyclodextrin are preferred as theorganic solvent for use in dissociating and extracting a compoundentrapped in the aqueous cyclodextrin phase from the cyclodextrin.Examples of such organic solvents include ethers such as diethyl ether,diisopropyl ether, and diisoamyl ether; hydrocarbons such as liquefiedpropane gas (LPG), liquefied butane gas, pentanes, hexanes, heptanes,and mesitylene; and halogenated hydrocarbons such as dichloromethane.Incidentally, in the case of an extraction solvent highly volatile witha boiling point of at least ordinary temperature and comparativelyeasily soluble in the aqueous solution of cyclodextrin like diethylether, it is preferred to repeat at suitable time intervals theprocedure of effecting extraction by stirring for a period of a fewseconds to several tens of seconds after addition of the extractionsolvent and then recovering the resulting organic solvent layer. In thiscase, as the extraction solvent in continuing the operation afterrecovery of the solvent layer, either virgin solvent may be replenished,or the solvent separated from the compound(s) as the object(s) ofseparation through distillation or the like of the solvent layer may bereused

[0029] When a compound entrapped in the aqueous cyclodextrin phasehardly migrates into the organic phase of extraction solvent or takestime for such migration, a saturating amount of a salt such as sodiumchloride, potassium chloride or sodium sulfate may be dissolved in theaqueous cyclodextrin phase to facilitate migration of the includedcompound into the organic phase of extraction solvent. This is believedto be so because the solubility of the compound entrapped in the aqueousphase is lowered due to a salting-out effect.

[0030] Distillation may be used for separating the extracted organiccompound from the organic phase of extraction solvent. The organic phaseof extraction solvent wherein the compound to be separated is extractedis transferred to a distillation unit, wherein the compound to beseparated is concentrated. The extraction solvent separated bydistillation may be repeatedly used for extraction. This can reduce theconsumption of the extraction solvent.

[0031] When a low-boiling solvent boiling below ordinary temperature,e.g., liquefied petroleum gas such as liquefied propane gas (LPG) orliquefied butane gas, is used as the extraction solvent, a raw materialcontaining a compound(s) to be separated therefrom and an aqueoussolution of inclusion-complexing agent are placed in a reaction vesselsuch as a U-shaped tube or an H-shaped tube in an inclusion separatorprovided with a pressurizing means, e.g., an apparatus having a reactionvessel placed in an autoclave, and the low-boiling solvent is thenplaced in the reaction vessel under pressure, followed by stirring toperform a separation operation. After the separation operation, theseparator is depressurized to recover the vapor of the low-boilingsolvent. During the course of depressurization, heat being generatedduring liquefaction of the low-boiling solvent vapor throughpressurization may be utilized as an (ancillary) means for preventingtemperature drop of the organic phase and the aqueous phase in thereaction vessel in keeping with evaporation of the low-boiling solvent(means particularly for preventing the aqueous phase from freezing). Theliquefied low-boiling solvent can be reused as the extraction solvent.The extracted organic compound(s) remaining in the reaction vessel isrecovered. Alternatively, the organic phase after the extractionoperation may be first withdrawn from the reaction vessel into apressure vessel from which the low-boiling solvent vapor is recovered,instead of direct recovery of the low-boiling solvent vapor from thereaction vessel. In this case as well, heat being generated duringpressurization and liquefaction of the low-boiling solvent vapor may ofcourse be used as an (ancillary) means for preventing temperature dropof the residual organic phase(s) and the aqueous phase. Advantages ofusing a low-boiling solvent boiling below ordinary temperature lie inthat a great difference in boiling point between a compound as an objectof separation like a xylene isomer and an extraction solvent hardlyallows the low-boiling solvent to mix in the separated compound, and inthat a large-scale and elaborate distillation apparatus may be dispensedwith in performing an industrial separation process according to thepresent invention.

[0032] Examples of other inclusion-complexing agents includewater-soluble cyclophanes (Kiichi Takemoto, Mikiji Miyata & KeiichiKimura, “Inclusion Compounds—from Basics to Future Technologies—,”Edition 1, published by Tokyo Kagaku Dozin Co., Ltd. on Jun. 27, 1989,pp. 26-27), water-soluble calixarenes (Kiichi Takemoto, Mikiji Miyata &Keiichi Kimura, “Inclusion Compounds—from Basics to FutureTechnologies—,” Edition 1, published by Tokyo Kagaku Dozin Co., Ltd. onJun. 27, 1989, p. 32), etc. It is further believed that water-solublepolymolecular host compounds difficultly soluble in any organic solventcan be used. It has already been found out that a wide variety oforganic compounds including tetrasubstituted benzenes such as durene areincluded in such inclusion-complexing agents. Water-soluble cyclophanesare cyclized compounds formed, for example, by alternately bonding aplurality of (di)phenylene groups to a plurality of alkylene groups viaquaternary ammonium, tertiary sulfonium ormonohydroxyammonio-hydroxyethylene groups, provided that the(di)phenylene groups may be modified with hydrophilic groups such assulfonic groups either in a free acid form or in a salt form.Water-soluble calixarenes are cyclized compounds formed by alternatelybonding a plurality of phenolic rings with hydrophilic groups such assulfonic groups either in a free acid form or in a salt form, at theiro-positions, to a plurality of methylene groups (generally constitutedof 4 to 8 phenolic rings and 4 to 8 methylene groups), provided that thehydrogen atoms of the phenolic hydroxyl groups may each be substitutedwith a variety of group.

[0033]FIG. 1 is a conceptual cross-sectional view illustrating anexample of reaction vessel in the basic inclusion separator of thepresent invention that may be used in the method of the presentinvention. The reaction vessel of FIG. 1 is made up of a squarishU-shaped tube 1. FIG. 1 should be considered conceptual because thedimensional ratios and the like in FIG. 1 do not necessarily representactual values. Although a diaphragm 2 allowing an aqueous solution ofinclusion-complexing agent to pass thereacross is drawn in FIG. 1, it isnot necessarily an indispensable element. This reaction vessel is firstcharged with an aqueous phase 3 of an aqueous solution ofinclusion-complexing agent, and then charged with an organic phase 4 ofraw material and an organic phase 5 of extraction solvent, followed bystirring. Alternatively, there may be adopted a procedure of chargingthe reaction vessel with the aqueous phase 3 and then the organic phase4 of raw material, stirring at this stage, subsequently charging it withthe organic phase 5 of extraction solvent, and further stirring. Sincethe amount of the organic phase 4 of raw material decreases with anincreasing amount of the organic phase 5 of extraction solvent asstirring is continued, at least part of the organic phase 5 ofextraction solvent may be withdrawn with replenishment of the organicphase 4 of raw material if necessary, and fresh extraction solvent maybe replenished as needed. Thereafter, the organic phase 5 of extractionsolvent is withdrawn as needed, and the organic phase (oil extract)remaining after removal of the extraction solvent is subjected again orrepeatedly to the method of the present invention if necessary toheighten the purity of a compound as an object of separation in the oilextract obtained from the organic phase of extraction solvent.Incidentally, the reaction vessels of inclusion separators of FIGS. 2and 3 used in the following Examples 1 to 9 and 11 to 38 arefundamentally the same as the reaction vessel of FIG. 1.

[0034]FIGS. 4, 5 and 6 are conceptual cross-sectional views illustratinganother example of reaction vessel in the basic inclusion separator ofthe present invention that may be used in the method of the presentinvention. FIG. 4 shows a state of using a raw material higher inspecific gravity than an aqueous phase and an extraction solvent lowerin specific gravity than the aqueous phase. FIG. 5 shows a state ofusing a raw material lower in specific gravity than an aqueous phase andan extraction solvent higher in specific gravity than the aqueous phase.FIG. 6 shows a state of using a raw material and an extraction solventboth higher in specific gravity than an aqueous phase. FIGS. 4, 5 and 6should be considered conceptual because the dimensional ratios and thelike in FIGS. 4, 5 and 6 do not represent the actual values. Althoughdiaphragms 32, 42 and 52 allowing an aqueous solution ofinclusion-complexing agent to pass thereacross are drawn in FIGS. 4, 5and 6, they are not necessarily indispensable elements. In FIGS. 4, 5and 6, numerals 31, 41 and 51 refer to an H-shaped tube (reactionvessel), 33, 43 and 53 to aqueous phases of aqueous solutions ofinclusion-complexing agents, 34, 44 and 54 to organic phases of rawmaterials, and 35, 45 and 55 to organic phases of extraction solvents.Specifically, a reaction vessel made up of an H-shaped tube is desirablyused when the specific gravity of raw material and/or extraction solventis higher than that of the aqueous solution of inclusion-complexingagent, and is operated in substantially the same manner as in the casewhere the reaction vessel of FIG. 1 is used. Incidentally, the reactionvessel of inclusion separator used in the following Example 10 isfundamentally the same as the reaction vessel of FIG. 5.

[0035] The number of branch tubes extended vertically in a reactionvessel is not limited to 2 but may be 3 or more, and is preferably 2 to8, more preferably 2 to 6, although it is varied depending on the kindof raw material and the like. A reaction vessel may have at least threebranch tubes, so that an aqueous phase of an aqueous solution ofinclusion-complexing agent can have at least three liquid-liquidinterfaces, one of which is an interface with an organic phase of rawmaterial, and the other two or more of which are respective interfaceswith at least two kinds of extraction solvents. In this case, if anydifference(s) in extraction selectivity exists between extractionsolvents that dissociate and extract compounds to be separated from therespective inclusion complexes [see, e.g., “oil extract” columns inTables showing results of Example 3 (n-heptane), Example 5 (n-hexane),Example 6 (mesitylene), Example 8 (diisopropyl ether), Example 9(diisoamyl ether) and Example 10 (dichloromethane)], the purities ofseparated compounds extracted into the respective extraction solventscan be improved by making the most of any such difference(s) inextraction selectivity to decrease the number of repetitions of themethod of the present invention for securing desired purities ofrespective compounds. Incidentally, when use is made of an extractionsolvent lower in specific gravity than an aqueous solution ofinclusion-complexing agent and an extraction solvent higher in specificgravity than the aqueous solution of inclusion-complexing agent, anH-shaped tube may be used Even if a plurality of compounds as thecomponents of raw material are not so different in complex formationconstant, the purpose of the present invention may possibly be attainedif a plurality of extraction solvents are different in extractionselectivity. In a reaction vessel having, e.g., at least four branchtubes, raw material may be put, for example, into two branch tubes withrespectively putting at least two kinds of extraction solvents into theother two or more branch tubes to perform the method of the presentinvention. Thus, a variety of embodiments are conceivable.

[0036] Each vertical tube of a variety of branched tube such as aU-shaped tube or an H-shaped tube may be not only circular but alsoeither elliptic or polygonal such as tetragonal in cross section. Thereaction vessel of the inclusion separator is not limited to branchedtubes, and may be, for example, in the form of a box-like vessel or acylinder with a bottom plate (which may be provided with a ceilingplate) provided with a vertical partition having an aperture at asuitable location thereof to form a plurality of compartments, providedthat the aperture may be provided with a diaphragm if necessary. Anaqueous solution of inclusion-complexing agent is allowed to passbetween the compartments via the aperture or the diaphragm.

[0037] Although magnetic stirrers were used in Examples, what isessential to stirring for performing the method of the present inventionmay be sufficient stirring at least neighborhoods of liquid-liquidinterfaces. Examples of stirring means include stirring with ultrasonicvibration, stirring with shaking (in forward and backward, leftward andrightward, upward and downward, and/or clockwise and counterclockwisedirections), stirring with a stirring rod having agitating blades, etc.Where diaphragms permitting flow thereacross of an aqueous solution ofinclusion-complexing agent are attached to a reaction vessel havingbranch tubes, there may be provided two flow paths making two branchtubes communicate with each other, and the two flow paths may beprovided with respective diaphragms and water jet pumps (preferably onthe downstream sides of the diaphragms). When two water jet pumps in theflow paths making two branch tubes communicate with each other areactuated to form water streams in mutually opposite directions whilesufficiently stirring at least neighborhoods of liquid-liquid interfacesin the branch tubes, the flow of an aqueous solution ofinclusion-complexing agent parted by two diaphragms can be promotedwhile preventing raw material from mixing with extraction solvent due tothe diaphragms to perform the extraction operation more efficiently. Ofcourse, such a technical idea can also apply to a case where thereaction vessel is provided with a plurality of compartments. Forexample, two apertures with short pipes as flow paths may be providedbetween two compartments, and may be provided with diaphragms and waterjet pumps in the same manner as described above. Alternatively, twowater propeller fans, which can send water in opposite directionsthrough apertures formed between two compartments and provided withrespective diaphragms, may be provided in the respective compartments toperform the extraction operation more efficiently.

EXAMPLES

[0038] The following Examples will more specifically illustrate thepresent invention, but should not be construed as limiting the scope ofthe invention. The compositions of raw material and oil extract wereanalyzed according to capillary gas chromatography. Figures in thefollowing Tables indicate the peak area percentages assigned torespective components based on the total of all peak areas for isomersin raw material and oil extract in each gas chromatogram. The followingTables show changes in the composition of components by inclusioncomplexation and dissociation-extraction. Incidentally, inclusioncomplexation and dissociation-extraction were effected at roomtemperature in all the following Examples.

[0039]FIG. 2 is a conceptual schematic cross-sectional view of aninclusion separator used in Examples 12 and 28, wherein the dimensionalratios and the like of elements do not represent actual ones. The insidediameter of two tubes in vertical direction (vertical tubes) of areaction vessel in the form of a squarish U-shaped tube 11 is 28 mm,while the inside diameter of a horizontal tube, which is connected withthe vertical tubes having respective bottom plates, is 18 mm. Theshortest distance between the two vertical tubes is 28 mm, and theheight of the vertical tubes is 230 mm. Two magnetic stirrers 18 areinstalled under the bottom of the reaction vessel of the U-shaped tube11, while two spinbars 16 are placed in the U-shaped tube 11 TheU-shaped tube 11 is sealed by putting plugs 17 therein after fed with anaqueous cyclodextrin phase 13, an organic phase 14 of raw material andan organic phase 15 of extraction solvent. Thereafter, the magneticstirrers 18 are worked to rotate the spinbars 16, thereby to effectstirring.

[0040]FIG. 3 is a conceptual schematic cross-sectional view of aninclusion separator used in Examples 1 to 9, 11, 13 to 27 and 29 to 38,wherein the dimensional ratios and the like of elements do not representactual ones. The inside diameter of two tubes in vertical direction(vertical tubes) of a reaction vessel in the form of a squarish U-shapedtube 21 is 23 mm, while the inside diameter of a horizontal tube is 30mm. The horizontal tube having side plates on both ends is connectedwith the vertical tubes, provided that portions thereof where spinbars26 are placed are flat. The shortest distance between the two verticaltubes is 60 mm, and the length ranging from the bottom of the reactionvessel of the U-shaped tube 21 to the tops of the two vertical tubes is100 mm. In FIG. 3, a diaphragm 22 made of filter paper or other materialis drawn, but is not used in some Examples. Two magnetic stirrers 28 areinstalled under the bottom of the reaction vessel of the U-shaped tube21, while the two spinbars 26 are placed in the U-shaped tube 21. TheU-shaped tube 21 is sealed by putting plugs 27 therein after fed with anaqueous cyclodextrin phase 23, an organic phase 24 of raw material andan organic phase 25 of extraction solvent. Thereafter, the magneticstirrers 28 are worked to rotate the spinbars 26, thereby to effectstirring. In Example 7, however, an aqueous cyclodextrin phase 23 and anorganic phase 24 of raw material were placed in the U-shaped tube 21, inwhich plugs 27 were then put, followed by stirring, while an extractionsolvent 26 was subsequently placed in the U-shaped tube 21 after theright plug was pulled out therefrom, followed by reattaching the rightplug and then stirring. Incidentally, the “squarish U-shaped tube” ofFIG. 2 or 3 will hereinafter referred to simply as the “U-shaped tube.”In Example 10 wherein dichloromethane higher in specific gravity than anaqueous cyclodextrin phase was used as extraction solvent, use was madeof an H-shaped tube, which was substantially the same as the U-shapedtube of FIG. 3 except for two vertical tubes alone elongated furtherdownward (the length of tubes ranging from the bottoms of thedownward-elongated tube portions to the tops of the upward-elongatedtube portions is 130 mm). Incidentally, it is a matter of course that anindustrial inclusion separator may be provided with a ceiling plateinstead of plugs, provided that feed and withdrawal of a raw material,an aqueous solution of inclusion-complexing agent and an extractionsolvent are done via pipings.

Example 1

[0041] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 15 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 15 ml of n-heptane was placed in theother vertical tube. Stirring was effected in such a manner that thexylene phase did not mix with the heptane phase. The composition ofxylene isomers extracted in the n-heptane phase after 2 hours is shownin Table 1. TABLE 1 Raw Material Oil Extract p-Xylene 49.8% 76.3%m-Xylene 50.2% 23.7%

Example 2

[0042]250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 15 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with filter paper. The composition ofxylene isomers extracted in the n-heptane phase after 1 hour is shown inTable 2. TABLE 2 Raw Material Oil Extract p-Xylene 49.8% 82.9% m-Xylene50.2% 17.1%

Example 3

[0043] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 6 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube while 6 ml of n-heptane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with filter paper.The composition of xylene isomers extracted in the n-heptane phase after2 hours is shown in Table 3. TABLE 3 Raw Material Oil ExtractEthylbenzene 15.4% 20.7% p-Xylene 18.7% 49.6% m-Xylene 44.2% 24.0%o-Xylene 21.7%  5.7%

Example 4

[0044] A solution containing 70 g of sodium chloride dissolved in 250 mlof a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrin mixture wasplaced in a U-shaped tube. 6 ml of mixed xylene (commercially availableproduct) was placed in one vertical tube of the U-shaped tube while 6 mlof n-hexane was placed in the other vertical tube. Vigorous stirring waseffected, provided that the bottom portion of the U-shaped tube waspartitioned with filter paper. The composition of xylene isomersextracted in the n-hexane phase after 2 hours is shown in Table 4. TABLE4 Raw Material Oil Extract Ethylbenzene 15.4% 22.0% p-Xylene 18.7% 54.7%m-Xylene 44.2% 20.1% o-Xylene 21.7%  3.2%

Example 5

[0045] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 6 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube while 6 ml of n-hexane was placed in the othervertical tube. Stirring was effected in such a manner that the xylenephase did not mix with the heptane phase. The composition of xyleneisomers extracted in the n-hexane phase after 2 hours is shown in Table5. TABLE 5 Raw Material Oil Extract Ethylbenzene 15.4% 19.9% p-Xylene18.7% 43.9% m-Xylene 44.2% 26.8% o-Xylene 21.7%  9.4%

Example 6

[0046] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 6 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube while 6 ml of mesitylene was placed in theother vertical tube. Stirring was effected in such a manner that thexylene phase did not mix with the mesitylene phase. The composition ofxylene isomers extracted in the mesitylene phase after 2 hours is shownin Table 6. TABLE 6 Raw Material Oil Extract Ethylbenzene 15.4% 19.2%p-Xylene 18.7% 42.4% m-Xylene 44.2% 28.7% o-Xylene 21.7%  9.7%

Example 7

[0047] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube. Vigorous stirring was effected, provided thatthe bottom portion of the U-shaped tube was partitioned with filterpaper. After 20 minutes, 5 ml of diethyl ether was added to the othervertical tube of the U-shaped tube, and both spinbars were revolved toeffect 5 seconds of vigorous stirring. Thereafter, the liquids wereallowed to stand (about 30-60 seconds) until the aqueous cyclodextrinphase was separated from the ether phase. The ether phase was recovered.The composition of xylene isomers extracted in the ether phase is shownin Table 7. Incidentally, initial 20 minutes of stirring was anoperation of entrapment into the aqueous phase from mixed xylene throughcomplex formation, while subsequent 5 seconds of stirring was anoperation of extracting substances migrated to the aqueous phase intothe ether phase through complex dissociation. The short stirring time of5 seconds was due to a difficulty in phase separation between theaqueous phase and the ether phase if stirred for a long time, becausediethyl ether is a little soluble in water. TABLE 7 Raw Material OilExtract Ethylbenzene 15.4% 20.8% p-Xylene 18.7% 50.2% m-Xylene 44.2%24.6% o-Xylene 21.7%  4.5%

Example 8

[0048] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube while 10 ml of diisopropyl ether was placed inthe other vertical tube. Vigorous stirring was effected with bothspinbars, provided that the bottom portion of the U-shaped tube waspartitioned with filter paper. The composition of xylene isomersextracted in the diisopropyl ether phase after 30 minutes is shown inTable 8. TABLE 8 Raw Material Oil Extract Ethylbenzene 15.4% 20.0%p-Xylene 18.7% 46.7% m-Xylene 44.2% 24.4% o-Xylene 21.7%  8.9%

Example 9

[0049] 260 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube while 10 ml of diisoamyl ether was placed inthe other vertical tube. Vigorous stirring was effected, provided thatthe bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of xylene isomers extracted in the diisoamylether phase after 30 minutes is shown in Table 9. TABLE 9 Raw MaterialOil Extract Ethylbenzene 15.4% 20.4% p-Xylene 18.7% 41.5% m-Xylene 44.2%26.3% o-Xylene 21.7% 11.8%

Example 10

[0050] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in an H-shaped tube. 10 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the H-shaped tube while 5 ml of dichloromethane was placed inthe other vertical tube. Vigorous starring was effected, provided thatthe bottom portion of the H-shaped tube was partitioned with filterpaper. The composition of xylene isomers extracted in thedichloromethane phase after 1 hour is shown in Table 10. TABLE 10 RawMaterial Oil Extract Ethylbenzene 15.4% 21.0% p-Xylene 18.7% 52.3%m-Xylene 44.2% 22.2% o-Xylene 21.7%  4.5%

Example 11

[0051] 250 ml of a 10 wt. % aqueous solution of amaltosyl-β-cyclodextrin mixture was placed in a U-shaped tube. 20 ml ofmixed xylene (commercially available product) was placed in one verticaltube of the U-shaped tube while 20 ml of n-heptane was placed in theother vertical tube. Stirring was effected in such a manner that thexylene phase did not mix with the heptane phase. The composition ofxylene isomers extracted in the n-heptane phase after 1 hour is shown inTable 11. TABLE 11 Raw Material Oil Extract Ethylbenzene 15.5% 13.0%p-Xylene 18.6% 17.8% m-Xylene 43.2% 30.9% o-Xylene 22.7% 38.2%

Example 12

[0052] 100 ml of a 10 wt. % aqueous solution of2,6-dimethyl-α-cyclodextrin was placed in a U-shaped tube. 5 ml of mixedxylene (commercially available product) was placed in one vertical tubeof the U-shaped tube while 5 ml of n-heptane was placed in the othervertical tube. Stirring was effected in such a manner that the xylenephase did not mix with the heptane phase. The composition of xyleneisomers extracted in the n-heptane phase after 1 hour is shown in Table12. TABLE 12 Raw Material Oil Extract Ethylbenzene 15.4% 26.0% p-Xylene18.7% 17.5% m-Xylene 44.2% 42.7% o-Xylene 21.7% 13.8%

Example 13

[0053] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 6 ml of amixture of o-nitrotoluene, m-nitrotoluene and p-nitrotoluene was placedin one vertical tube of the U-shaped tube while 6 ml of n-heptane wasplaced in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of nitrotoluene isomers extracted inthe n-heptane phase after 2 hours is shown in Table 13. TABLE 13 RawMaterial Oil Extract o-Nitrotoluene 34.6% 13.6% m-Nitrotoluene 33.0%27.7% p-Nitrotoluene 32.4% 58.7%

Example 14

[0054] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 1 ml of amixture of o-chlorotoluene, m-chlorotoluene and p-chlorotoluene wasplaced in one vertical tube of the U-shaped tube while 10 ml ofn-heptane was placed in the other vertical tube. Vigorous stirring waseffected, provided that the bottom portion of the U-shaped tube waspartitioned with filter paper. The composition of chlorotoluene isomersextracted in the n-heptane phase after 2 hours is shown in Table 14.TABLE 14 Raw Material Oil Extract o-Chlorotoluene 33.5% 17.1%m-Chlorotoluene 33.0% 29.5% p-Chlorotoluene 33.5% 53.3%

Example 15

[0055] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 0.5 ml ofa mixture of o-chlorobenzotrifluoride, m-chlorobenzotrifluoride andp-chlorobenzotrifluoride was placed in one vertical tube of the U-shapedtube while 5 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with filter paper. The composition ofchlorobenzotrifluoride isomers extracted in the n-heptane phase after 2hours is shown in Table 15. TABLE 15 Raw Material Oil Extracto-Chlorobenzotrifluoride 33.2% 31.8% m-Chlorobenzotrifluoride 29.6%14.1% p-Chlorobenzotrifluoride 37.1% 54.1%

Example 16

[0056] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 1.8 ml ofa mixture of 3 trimethylbenzene isomers, i.e., mesitylene, pseudocumeneand hemimellitene, was placed in one vertical tube of the U-shaped tubewhile 5 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition oftrimethylbenzene isomers extracted in the n-heptane phase after 3 hoursis shown in Table 16. TABLE 16 Raw Material Oil Extract Mesitylene 33.0%16.2% Pseudocumene 34.0% 17.9% Hemimellitene 33.0% 65.9%

Example 17

[0057] 250 ml of a 10 wt. % aqueous solution of a maltosyl-62-cyclodextrin mixture was placed in a U-shaped tube. 1.8 ml of a mixtureof 3 trimethylbenzene isomers, i.e., mesitylene, pseudocumene andhemimellitene, was placed in one vertical tube of the U-shaped tubewhile 5 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition oftrimethylbenzene isomers extracted in the n-heptane phase after 3 hoursis shown in Table 17. TABLE 17 Raw Material Oil Extract Mesitylene 33.0%18.4% Pseudocumene 34.0% 59.5% Hemimellitene 33.0% 22.1%

Example 18

[0058] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 6 ml of amixture of 3 trichlorobenzene isomers, i.e., 1,3,5-trichlorobenzene,1,2,4-trichlorobenzene and 1,2,3-trichlorobenzene, was placed in onevertical tube of the U-shaped tube while 6 ml of n-heptane was placed inthe other vertical tube. Vigorous stirring was effected, provided thatthe bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of trichlorobenzene isomers extracted in then-heptane phase after 1 hour is shown in Table 18. TABLE 18 Raw MaterialOil Extract 1,3,5-Trichlorobenzene 34.3% 23.8% 1,2,4-Trichlorobenzene33.0% 21.3% 1,2,3-Trichlorobenzene 32.7% 54.9%

Example 19

[0059] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 6 ml of an-heptane solution of 3 dimethylphenol isomers, i.e.,2,3-dimethylphenol, 3,4-dimethylphenol and 3,5-dimethylphenol, wasplaced in one vertical tube of the U-shaped tube while 6 ml of n-heptanewas placed in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of dimethylphenol isomers extractedin the n-heptane phase after 2 hours is shown in Table 19. TABLE 19 RawMaterial Oil Extract 3,5-Dimethylphenol 31.4% 23.2% 2,3-Dimethylphenol34.5% 51.5% 3,4-Dimethylphenol 34.1% 25.3%

Example 20

[0060] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 2 ml of amixture of 3 nitroxylene isomers, i.e., 2-nitro-m-xylene,4-nitro-m-xylene and 5-nitro-m-xylene, was placed in one vertical tubeof the U-shaped tube while 5 ml of n-heptane was placed in the othervertical tube. Vigorous stirring was effected, provided that the bottomportion of the U-shaped tube was partitioned with filter paper. Thecomposition of nitroxylene isomers extracted in the n-heptane phaseafter 2 hours is shown in Table 20. TABLE 20 Raw Material Oil Extract2-Nitro-m-xylene 34.8% 72.0% 4-Nitro-m-xylene 32.5%  9.5%5-Nitro-m-xylene 32.7% 18.6%

Example 21

[0061] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 0.5 ml ofa mixture of 1-methylnaphthalene and 2-methylnaphthalene was placed inone vertical tube of the U-shaped tube while 3 ml of n-heptane wasplaced in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of methylnaphthalene isomersextracted in the n-heptane phase after 2 hours is shown in Table 21.TABLE 21 Raw Material Oil Extract 1-Methylnaphthalene 50.4%  7.8%2-Methylnaphthalene 49.6% 92.2%

Example 22

[0062] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 0.5 ml ofa dimethylnaphthalene mixture (commercially available product) wasplaced in one vertical tube of the U-shaped tube while 3 ml of n-heptanewas placed in the other vertical tube. Vigorous starring was effected,provided that the bottom portion of the U shaped tube was partitionedwith filter paper. The composition of dimethylnaphthalene isomersextracted in the n-heptane phase after 90 minutes is shown in Table 22.TABLE 22 Raw Material Oil Extract 2,6-Dimethylnaphthalene 10.6% 42.2%2,7-Dimethylnaphthalene 13.5%  4.0% Other Dimethylnaphthalenes 75.9%53.8%

Example 23

[0063] 250 ml of a 10 wt. % aqueous solution of amaltosyl-β-cyclodextrin mixture was placed in a U-shaped tube. 1 ml of amixture of 2,6-diisopropylnaphthalene and 2,7-diisopropylnaphthalene wasplaced in one vertical tube of the U-shaped tube while 5 ml of n-heptanewas placed in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of diisopropylnaphthalene isomersextracted in the n-heptane phase after 2 hours is shown in Table 23.TABLE 23 Raw Material Oil Extract 2,6-Diisopropylnaphthalene 49.2% 68.2%2,7-Diisopropylnaphthalene 50.8% 31.8%

Example 24

[0064] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 2 ml of amixture of 2-methylquinoline and 8-methylquinoline was placed in onevertical tube of the U-shaped tube while 10 ml of n-heptane was placedin the other vertical tube. Vigorous stirring was effected, providedthat the bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of methylquinoline isomers extracted in then-heptane phase after 1 hour is shown in Table 24. TABLE 24 Raw MaterialOil Extract 2-Methylquinoline 48.8% 59.8% 8-Methylquinoline 51.2% 40.2%

Example 25

[0065] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 2 ml of amixture of 7-methylquinoline and 5-methylquinoline was placed in onevertical tube of the U-shaped tube while 10 ml of n-heptane was placedin the other vertical tube. Vigorous stirring was effected, providedthat the bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of methylquinoline isomers extracted in then-heptane phase after 1 hour is shown in Table 25. TABLE 25 Raw MaterialOil Extract 7-Methylquinoline 81.0% 86.9% 5-Methylquinoline 19.0% 13.1%

Example 26

[0066] 250 ml of a 20 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 15 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-hexane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with filter paper.The composition of xylene isomers extracted in the n-hexane phase after1 hour is shown in Table 26. TABLE 26 Raw Material Oil Extract p-Xylene49.8% 83.2% m-Xylene 50.2% 16.8%

Example 27

[0067] 250 ml of a 20 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 30 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 40 ml of n-pentane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with filter paper.After 30 minutes, stirring on the n-pentane phase side was stopped. Whenthe aqueous cyclodextrin phase was separated from the n-pentane phase,about 20 ml of the n-pentane solution of the n-pentane phase wastransferred to a distillation apparatus. Thereafter, stirring wascontinued in the U-shaped tube. On the other hand, extracted xyleneswere concentrated with the distillation apparatus, while n-pentanevaporized through distillation was cooled and liquefied, and thenreturned back to the n-pentane phase in the U-shaped tube. After about 5minutes, the same procedure as described above was performed. Theforegoing procedure was repeated. The composition of xylene isomersconcentrated in the distillation apparatus after 6 hours is shown inTable 27. TABLE 27 Raw Material Oil Extract p-Xylene 49.8% 80.8%m-Xylene 50.2% 19.2%

Example 28

[0068] 100 ml of a 10 wt. % aqueous solution of α-cyclodextrin dissolvedin water containing 10 wt. % sodium hydroxide was placed in a U-shapedtube. 20 ml of mixed xylene (commercially available product) was placedin one vertical tube of the U-shaped tube while 20 ml of n-heptane wasplaced in the other vertical tube. Stirring was effected in such amanner that the xylene phase did not mix with the heptane phase. Thecomposition of xylene isomers extracted in the n-heptane phase after 2hours is shown in TABLE 28 Raw Material Oil Extract Ethylbenzene 15.5%20.4% p-Xylene 18.6% 23.3% m-Xylene 43.2% 42.8% o-Xylene 22.7% 13.5%

Example 29

[0069] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 15 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-hexane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with a rayonnonwoven fabric. The composition of xylene isomers extracted in then-hexane phase after 1 hour is shown in Table 29. TABLE 29 Raw MaterialOil Extract p-Xylene 49.9% 71.0% m-Xylene 50.1% 29.0%

Example 30

[0070] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 15 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-hexane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with a glass fiberfilter. The composition of xylene isomers extracted in the n-hexanephase after 1 hour is shown in Table 30. TABLE 30 Raw Material OilExtract p-Xylene 49.9% 83.4% m-Xylene 50.1% 16.6%

Example 31

[0071] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 15 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-heptane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with a nylon netfilter. The composition of xylene isomers extracted in the n-heptanephase after 1 hour is shown in Table 31. TABLE 31 Raw Material OilExtract p-Xylene 50.0% 82.2% m-Xylene 50.0% 17.8%

Example 32

[0072] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 15 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-heptane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with a filterportion of glass filtration apparatus. The composition of xylene isomersextracted in the n-heptane phase after 1 hour is shown in Table 32.TABLE 32 Raw Material Oil Extract p-Xylene 50.0% 81.2% m-Xylene 50.0%18.8%

Example 33

[0073] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-heptane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with a stainlesssteel net. The composition of xylene extracted in the n-heptane phaseafter 1 hour is shown in Table 33. TABLE 33 Raw Material Oil Extractp-Xylene 50.0% 77.9% m-Xylene 50.0% 22.1%

Example 34

[0074] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml ofan about 1:1 mixture of p-xylene and m-xylene was placed in one verticaltube of the U-shaped tube while 10 ml of n-heptane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with a silk screenThe composition of xylene isomers extracted in the n-heptane phase after1 hour is shown in Table 34. TABLE 34 Raw Material Oil Extract p-Xylene49.9% 70.2% m-Xylene 50.1% 29.8%

Example 35

[0075] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture containing 69 g of potassium chloridewas placed in a U-shaped tube. 10 ml of an about 1:1 mixture of p-xyleneand m-xylene was placed in one vertical tube of the U-shaped tube while10 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with a nylon net filter. The composition of xyleneisomers extracted in the n-heptane phase after 1 hour is shown in Table35. TABLE 35 Raw Material Oil Extract p-Xylene 50.0% 88.1% m-Xylene50.0% 11.9%

Example 36

[0076] 230 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture containing 83 g of sodium sulfate wasplaced in a U-shaped tube. 10 ml of an about 1:1 mixture of p-xylene andm-xylene was placed in one vertical tube of the U-shaped tube while 10ml of n-heptane was placed in the other vertical tube. Vigorous stirringwas effected, provided that the bottom portion of the U-shaped tube waspartitioned with a nylon net filter. The composition of xylene isomersextracted in the n-heptane phase after 1 hour is shown in Table 36.TABLE 36 Raw Material Oil Extract p-Xylene 50.0% 87.5% m-Xylene 50.0%12.5%

Example 37

[0077] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml ofan about 1:1 mixture of (1S)-(−)-α-pinene and (1R)-(+)-α-pinene wasplaced in one vertical tube of the U-shaped tube while 10 ml ofn-heptane was placed in the other vertical tube. Vigorous stirring waseffected, provided that the bottom portion of the U-shaped tube waspartitioned with filter paper. The composition of a-pinene isomersextracted in the n-heptane phase after 90 minutes is shown in Table 37.TABLE 37 Raw Material Oil Extract (1S)-(−)-α-Pinene 49.5% 69.5%(1R)-(+)-α-Pinene 50.5% 30.5%

Example 38

[0078] 250 ml of a 10 wt. % aqueous solution of aglucosyl-α-cyclodextrin mixture was placed in a U-shaped tube. 10 ml of(±)-limonene was placed in one vertical tube of the U-shaped tube while10 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition of limoneneisomers extracted in the n-heptane phase after 90 minutes is shown inTable 38. TABLE 38 Raw Material Oil Extract (S)-(−)-Limonene 49.8% 42.2%(R)-(+)-Limonene 50.2% 57.8%

Industrial Applicability

[0079] An operation of selectively inclusion-complexing a compound by anaqueous solution of cyclodextrin and an operation of dissociating andrecovering the compound selectively entrapped by the aqueous solution ofcyclodextrin from the cyclodextrin have heretofore been performedseparately. According to the present invention, these operations can beconsecutively performed to make the whole separation process veryefficient.

1. A continuous and selective inclusion separation method characterizedin that, in a reaction system having at least two liquid-liquidinterfaces between an organic phase of raw material containing acompound(s) to be separated and an aqueous phase of an aqueous solutionof inclusion-complexing agent and between said aqueous phase and anorganic phase(s) of extraction solvent(s), said compound(s) to beseparated is entrapped into said aqueous phase through formation of aninclusion complex(es) of said inclusion-complexing agent with saidcompound(s), while said compound(s) is entrapped into said organicphase(s) of extraction solvent(s) through dissociation of said inclusioncomplex(es).
 2. A continuous and selective inclusion separation methodas claimed in claim 1, characterized in that a diaphragm easilypermeable to said aqueous solution of inclusion-complexing agent buthardly permeable to oil droplets of said organic phases is provided insaid aqueous phase to prevent the two or more organic phases from mixingwith each other even with vigorous stirring.
 3. A continuous andselective inclusion separation method as claimed in claim 1 or 2,characterized in that said inclusion-complexing agent is acyclodextrin(s).
 4. A continuous and selective inclusion separationmethod as claimed in claim 3, characterized in that said raw materialcontaining a compound(s) to be separated is a raw material selected fromthe group consisting of indole-containing mixtures, disubstitutedbenzene isomer mixtures, trisubstituted benzene isomer mixtures,2-methylquinoline-containing hydrocarbon oils,7-methylquinoline-containing mixtures,2,6-diisopropylnaphthalene-containing mixtures,2-methylnaphthalene-containing mixtures,2,6-dimethylnaphthalene-containing mixtures, and optical isomer mixturesof pinene, limonene, menthol, mandelic acid esters, or the like.
 5. Acontinuous and selective inclusion separation method as claimed in anyone of claims 1 to 4, characterized in that at least part of a solutionas the organic phase containing a compound extracted thereinto as anobject of separation is withdrawn and distilled to concentrate saidcompound, and the organic solvent separated by distillation is returnedback to the reaction system and reused as the extraction solvent.
 6. Aninclusion separator characterized by comprising a reaction vesselconstructed so as to allow an aqueous phase of an aqueous solution ofinclusion-complexing agent to form liquid-liquid interfaces with atleast two organic phases that are an organic phase of raw materialcontaining a compound(s) to be separated and an organic phase(s) ofextraction solvent(s), and stirring means for stirring at leastneighborhoods of the respective liquid-liquid interfaces.
 7. Aninclusion separator as claimed in claim 6, characterized in that adiaphragm easily permeable to said aqueous solution ofinclusion-complexing agent but hardly permeable to oil droplets of saidorganic phases is provided in an inner portion of said reaction vesselwherein said aqueous phase is positioned, whereby said at least twoorganic phases are prevented from mixing with each other via saidaqueous phase.